Chronic pelvic pain significantly affects the health of up to 10 percent of women with endometriosis (Stratton, Fertil Steril 2006;86: 1302). We have recently published the results of a randomized, prospective, placebo-controlled trial of raloxifene (180 mg daily) used by women with chronic pelvic pain and endometriosis. This study was one of the largest randomized studies of medical therapy for endometriosis and, unlike other studies of endometriosis and pain, adhered to stringent entry criteria, including only those with biopsy-proven disease. Unexpectedly, women treated with the selective estrogen-receptor modulator raloxifene experienced return of chronic pelvic pain sooner than those treated with placebo. As both groups had endometriosis in similar proportions at second surgery, these results suggested that interference with estrogen action was related to pain threshold, lowering it in some such that their pain returned sooner. Diagnosis of endometriosis is done at a surgical procedure. One persistent issue in surgical diagnosis is whether histologic confirmation of the disease should be obtained, given the variable appearance of lesions. Stratton and Stegmann have correlated biopsy results with lesion appearance in two different ways. In the first study, we reported on the histologic confirmation given varying lesion characteristics, illustrating that no single color was associated with endometriosis and that surgeons should biopsy any suspicious lesion. Overall, it appears that single color lesions had similar frequencies of biopsy-confirmed endometriosis (59 to 62%). Only lesions with multiple colors had a significantly higher percentage of positive biopsies (76%). Of subtle lesions, 60% who only these type of lesions had endometriosis and of these, 40% of women who had only small, subtle lesions had biopsy-proven endometriosis. Mixed color lesions and endometriomas were the only two lesion types that were more commonly biopsy-proven (78%). In a second study, they created a logistic model to predict endometriosis. This model identified characteristics which indicated a high and low probability of biopsy-proven endometriosis. It was useful as a guide in choosing appropriate lesions for biopsy, but should not be used as a substitute for histologic confirmation. Stratton and her team of surgeons have continued to describe other causes of chronic pain in women with endometriosis, such as adenomyosis, appendiceal disease, or obdurator hernia. Of the women surveyed by the Endometriosis Association, 4,334 Endometriosis Association members reported surgically diagnosed endometriosis. In a subset of these women (1,160) reporting primarily having pelvic pain (95%), many women had tried 3+ medical treatments (46%) and had at least 3 surgical procedures (42%). Despite reporting various treatments as helpful, women used many different types and endured symptoms for an average of two decades, indicating the profound effect of endometriosis on womens health. To better understand endometriosis, chronic pelvic pain and its treatment, we have analyzed a survey of 4,334 Endometriosis Association members reporting surgically diagnosed endometriosis. We have investigated whether the first doctor seen and adolescent onset of symptoms impact the diagnostic process of endometriosis. Almost all respondents reported pelvic pain with 50% first consulting a gynecologist and 45% a generalist for symptoms of endometriosis. Women and girls who reported seeing a gynecologist first for symptoms of endometriosis were more likely to have a shorter time to diagnosis, see fewer physicians, and report a better experience overall with their physicians. The majority reported onset of symptoms during adolescence, who reported a longer time and a worse experience while obtaining a diagnosis. Sinaii and Stratton have also considered the relationship between disease severity and patient characteristics in endometriosis by analyzing questionnaires from 1,000 women in the Oxford Endometriosis Gene (OXEGENE) Study. Women were assigned to Group I (rAFS Stage I-II, n=423) or Group II (rAFS Stages III-IV, n=517). The most common symptoms leading to a diagnosis were dysmenorrhea and pelvic pain. Dyspareunia and depression were more common in Group I. In Group II, sub-fertility and an ovarian mass more commonly led to a diagnosis. Sub-fertility remained more common in Group II throughout reproductive life, but birth and miscarriage rates were similar. This study shows differences in characteristics of women with different stages of endometriosis, which may aid future clinical and epidemiological studies. Remarkably, the time to diagnosis was similar between women with different stages of disease. Chronic stress and depression blunt the ACTH and cortisol response curves following Corticotropic-Releasing Hormone stimulation. Patients with chronic pelvic pain experience both and are at risk of having an altered response. In addition, women with chronic pelvic pain may also have other regional pain syndromes like migraine headaches. We have recently hypothesized that these two chronic, debilitating conditions might co-occur. In our preliminary review of patients enrolled in the clinical trial, at least two thirds of women with chronic pelvic pain have migraine headaches that appear to be independent of endometriosis diagnosis. We will examine whether quality-of-life is lowered, beyond that due to pelvic pain alone. If migraine headache is common in women with chronic pelvic pain, regardless of the presence of endometriosis, it may contribute to disability of those with both conditions and may suggest a common pathophysiology. In the coming year, we will continue examining aspects of the health of women with endometriosis by analyzing the Endometriosis Association Survey, continue efforts to define the pain outcomes in endometriosis clinical trials, and conduct analyses of endocrine responses in women with chronic pelvic pain related to endometriosis to determine whether there may be altered stress responses in chronic pelvic pain.